3.3 kb gene, 3 exons

600 bp

precursor 74 amino acids, mature peptide 51 aminoacids, trefoil domain from aminoacids residues 24 to 67. The 74 aminoacids TFF3 protein precusor contains a signal peptide. The mature secreted peptide of 51 aminoacids contains one TFF (TreFoil Factor) domain and one acidic C-terminal domain. The acidic C-terminal domain contains a free cystein residue that promotes homodimerization and heterodimerization.

Under normal conditions TFF3 is expressed by gobblet cell of the intesine and the colon. TFF3 expression was found in human respiratory tract, human conjunctival goblet cells and in human salivarygland. In addition TFF3 peptive was found in human hypothalamus.

In secreterory epithelia TFF3 is expressed by mucin-producing cells. In the brain TFF3 is expressed by a population of neurons of the human hypothamic paraventricular and supraoptic nuclei.

TFF3 promotes migration of epithelial cells in vitro and enhance mucosal healing and epithelial restitutions in vivo in the gastrointestinal mucosa. TFF3 deficient mice aresuceptible to colonic injury induced by standard agents and restitution is impaired. In addition TFF3 deficient mice have an increase in colonocyte apoptosis. The protective action of TFF3 involves activation of both EGF-R and PI3K-Akt pathways. The role of TFF3 in the brain is not clear yet.

TFF3 belongs to the Trefoil peptide family (TFF) and possesse one TFF1 motif homologous to the TFF motif of TFF1 and TFF2. The TFF motif spans about 40 amino acids and is formed by 6 conserved cysteines residues involved in specific disulfites bridges.